RELATION BETWEEN SKIN-CANCER, HUMORAL RESPONSES TO HUMAN PAPILLOMAVIRUSES, AND HLA CLASS-II MOLECULES IN RENAL-TRANSPLANT RECIPIENTS

Human papillomaviruses (HPV), especially the epidermodysplasia verruci formis (EV)-associated HPV 5, 8, 14, 17, 20, and 47, are thought to pl ay a role in the pathogenesis of some skin cancers in recipients of re nal allografts. MHC class I and class II genes are involved in the cel lular immune response to viral and tumor Ag. Little is known about hum oral responses to HPV in recipients with and without skin cancer. We i nvestigated the prevalance of antibodies to the early (E) protein E7 a nd the major capsid late (L) protein L1 of HPV 8. In addition, we stud ied the association of HLA class II molecules with these antibody resp onses. The E7 and L1 open reading frames of HPV 8 were bacterially exp ressed as beta-galactosidase fusion proteins, which were purified by p reparative gel electrophoresis. Serum samples from 36 renal transplant recipients with and 91 recipients without skin cancer were screened f or the presence of IgG and IgM antibodies to HPV 8 E7 and L1, by Weste rn blot analysis. The detection of anti-HPV 8 L1 antibodies represents the immune response to HPV 8 and possibly other EV-associated HPV, be cause cross-reactivity between the representatives of this HPV subgenu s can occur. The antibody responses to HLA Ag were used as controls. R ecipients who had IgM antibodies but no IgG antibodies to L1 of HPV 8 (patients with no apparent class switch from IgM to IgG) had skin canc er in 50% of cases, whereas recipients who produced IgG antibodies (pa tients with an apparently good humoral response to L1 of HPV 8) had sk in cancer in only 18% of cases. The estimated relative risk of skin ca ncer in recipients with no class switch, compared with the risk in tho se with a good humoral response, was 4.5 (95% confidence interval, 1.1 to 18.1). We found no association between the antibody response to HL AAg and the occurrence of skin cancer. A strong linkage between the ab sent class switch of antibody production in response to L1 of HPV 8 an d HLA-DR7 was observed (relative risk, 26.2). Renal transplant recipie nts who have no apparent class switch from IgM to IgG production in re sponse to Ag encoded by L1 of HPV 8 or possibly other EV-associated HP V are at an increased risk of skin cancer. The association with HLA-DR 7 indicates a genetic control of skin cancer development or regression , involving genes in the class II region of the MHC.